For families of children with food allergies, stepping outside each morning takes courage.
Every surface, every playground structure and every picnic table is a potential minefield. Young children's hands, seemingly innocuous foods and even the dirt on the ground are all suspect. Accidental exposure to allergens like peanuts can quickly turn into a life-or-death scenario and a trip to the emergency room.
This is the nerve-wracking reality for millions of families in the U.S. that have children with a food allergy -- more than one-third of them have a history of severe allergic reactions. And while the majority are told it's a life-long condition without a cure, more and more families are turning to a new treatment that's slowly gaining traction in the medical community.
Immunotherapy involves introducing tiny doses of food allergens in a controlled environment in order to build a resistance. Over time, that amount can be safely ramped up until patients -- who previously viewed peanuts as poison -- can knock back a few peanut M&Ms without trouble.
Many of the clinical trials focus specifically on oral immunotherapy for children, though the treatment has been shown to work on adults as well.
With several years of increasingly convincing research showing it's an effective and safe treatment option, dozens of immunotherapy clinics are popping up throughout the country. Each one brings the promise of a long-lasting reprieve from the dangers of living with a food allergy.
But some physicians remain uneasy, saying that immunotherapy is still in a burgeoning phase without the regulatory approvals and protocols needed to ensure it is safe, consistent and effective. Clinics are providing the treatment is divergent ways, and researchers caution that neither patient safety nor built-up immunity are guarantees.
Despite the uncertainty, many families are desperate, and choose to go through immunotherapy in order to protect their children from the dangers of simply going outside.
A rough start
Discovering a food allergy is a life-changing moment, and it typically happens by accident.
Charity Brockman, a mother living in Thousand Oaks, said she remembers the frightening moment around 2005 when her daughter Rachel had a horrible reaction to a peanut butter and jelly sandwich. She had no idea how severe food allergies could be, realizing later that it meant a life of scouring the house for any peanut contamination and carrying shots of epinephrine, better known as EpiPens, in order to save Rachel's life if she had a severe reaction.
"There's the life-threatening aspect, there is accidental consumption and there are kids dying here in the United States, which I did not know," Brockman said.
Practically, that meant Rachel had to grow up in a sort of bubble. Sitting at nut-free tables, bringing her own cake to birthday parties and eating separately from other kids all became daily practices, and spotting a single person with peanut butter during an outing meant Brockman would have to make a judgment call on whether to drop everything and go home.
"The stakes are so high," she said. "The fear of death was looming over us at all times."
With Rachel now 15 and in high school, Brockman said it's become increasingly difficult to stay tethered to her child at all times and control her environment. Seeking a solution, she discovered a local program offering oral immunotherapy for peanut allergy patients and jumped on the opportunity.
Right out the gate, Brockman said it was fraught with challenges. The staff running the program insisted that Rachel eat peanuts to induce a reaction before beginning treatment, despite the family knowing full well that she was allergic.
"I tried so hard to say, 'Can we just take out that one aspect?'" she said. "I said I would rather take that chance and have her go through all of this for nothing then have her go into a reaction that would be problematic."
What followed was a harrowing experience, including six straight hours of dry heaving and a full 24-hour period of intense physical reactions. Brockman said Rachel described it as a feeling of "impending doom," and that she was going to die. The resulting trauma lingered, and Rachel had panic attacks, going to urgent care with allergic reactions that weren't really happening.
Not only that, it was four long months of anxiety for little progress, Brockman said. Rachel could still barely tolerate a small dusting of peanut flour at the bottom of a little plastic cup.
"The anxiety for the whole time after that initial experience was just horrible, absolutely horrible. She was developing all these ticks, checking her pulse multiple times -- she would check it five times in five minutes and just a whole series of anxiety-related problems started to crop up."
Brockman admits it sounds crazy, but she and Rachel decided to try again. A nurse practitioner who worked on numerous oral immunotherapy trials at Stanford had just opened a clinic in Burbank, promising accelerated progress and flexible dosing to avoid a reaction. It took only eight weeks until Rachel could tolerate eating two peanuts.
"I cannot even tell you what a difference that has made -- it was night and day," Brockman said. "She went from her maintenance dose, agonizing over that tiny bit of powder each day, to eating two peanut M&Ms."
A local clinic with global appeal
Depending on who you talk to, the growing availability of oral immunotherapy in routine clinical practice may have outpaced the research and a badly needed medical consensus on how to carry out the treatment.
But with so much desperation and demand, there are now an estimated 75 to 100 clinics in the U.S. that have opted to side-step the ongoing debate and start offering some form of immunotherapy. Among those pioneers is Whitney Block, who opened her first clinic in Redwood City in 2017 and recently expanded into Southern California with a second location in Burbank, where she successfully treated Rachel.
Block had a head start over other clinics in many ways, working as a nurse practitioner on more than 20 food allergy research trials led by Stanford University, including at El Camino Hospital in Mountain View, over the course of six years. She agreed that patients are bound to see variance between clinics because there is no standardized way to do oral immunotherapy. That's why she believes her practical experience and intuition sets her apart.
"I felt like I had the 'boots on the ground' experience," Block said. "I'm more comfortable than even a lot of allergists out there to run this kind of clinic, because they don't have the in-person experience treating hundreds of kids in research trials."
Block has since parted ways with Stanford and left her private practice in Walnut Creek in order to focus solely on food allergy treatment, citing a growing demand. Patients from the East Coast were among her first clients, and she recently treated a patient living in Abu Dhabi who went through 12 hours of international travel multiple times to receive treatment.
Families interviewed by the Voice since 2015 have had glowing praise for Block, calling her a calming presence during what could easily be a frightening visit every two weeks. Counting herself among those happy customers is Alexis Wittkampf, a Belmont resident with two young daughters, one allergic to peanuts and the other allergic to cashews and eggs.
Trips to the Redwood City clinic, across from Kaiser Permanente's hospital campus, feel more like a fun excursion than a doctor's appointment, with the two girls running in and met by big hugs from the staff. Tolerating a new dose means eating mouthfuls of chocolate pudding followed by a monitoring period, and then they're out the door until the next visit two weeks later.
"Whitney cares so much about the kids and about our family and how we're doing that I literally entrust my kids' lives to her, I really do," Wittkampf said. "I just feel like they really care and love us, and that is very different than an allergist."
Like Brockman, Wittkampf's introduction to immunotherapy was a disappointment. Her eldest daughter, Emma, went through a clinical trial that had sluggish results and also began with an induced reaction. Less than half a peanut, she said, and Emma was vomiting and breaking out in hives. It took two EpiPens, an IV and a breathing mask to stabilize her.
Giving it another chance felt like the right move, Wittkampf said, if only because a lifetime of hypervigilance didn't seem like much of an alternative. Wiping down surfaces, quizzing chefs about meals and relying on others creates such a high-stress environment that it leaves her in a perpetual "mother bear" mode, she said, barraged by perceived threats against her children.
"Oral immunotherapy is risky, yes, but it's risky not to do it," Wittkampf said. "Doing nothing is terrifying, because you're just hoping they don't get a trace."
Wittkampf said her eventual switch to Block's clinic was the right choice, with Emma on track to tolerate a dose of two peanuts by the end of this year. Her younger daughter, Maya, is already at her so-called maintenance dose for cashews, and is up to eating one-third of an egg per day. The hope is that one day her daughters will be able to visit an ice cream shop without fear and order ice cream for the first time in their lives.
"I know it sounds ridiculous, but it's hard when their friends can do it but they can't. They could die," she said.
Lingering safety concerns
Amid the recent proliferation of clinics aimed at treating food allergies, many allergists and pediatricians are still recommending caution. And Whitney's clinic is the exception to the rule -- of the thousands of allergists practicing in America, only a tiny fraction are doing immunotherapy.
Dr. Edwin Kim, who has authored studies on immunotherapy since 2011, said he worries that allergists are jumping the gun by prematurely offering the treatment to patients without fully disclosing the risks of an accidental reaction. He also points out that many studies show 20% of the participants don't get the protection that purportedly comes from oral immunotherapy.
"If I'm the allergist, how do I tell the person eye-to-eye that their child is safe?" he said. "Don't get me wrong -- this is amazing stuff, but there needs to be a full disclosure. People need to be clear on what we know and what we don't know, and what they're getting into with this."
Among the misconceptions is the idea that oral immunotherapy offers a permanent cure to food allergies, when in reality it provides a much higher tolerance that takes upkeep. Research shows a vast majority of patients will have to continue taking a "maintenance" dose of the food allergen every single day for the rest of their lives in order to keep that resistance, and must avoid strenuous physical activity right after taking a dose.
What's more, Kim said immunotherapy is being done in a way that feels like the Wild West, with each clinic adopting their own dose sizes, pacing and treatment protocols. One particular regimen designed by the biotech company Aimmune to treat peanut allergies -- called AR101 -- is currently undergoing a review by the FDA, which Kim said will give patients a badly-needed level of assurance.
"My party line has always been patience -- hang in there, we are really close to getting something out there to patients," Kim said. "But the last thing we want to do is have people do it on their own and set it back."
Dr. Paul Turner, a researcher at Imperial College London, conceded in a report last month that the "horse has already bolted" with regards to oral immunotherapy, and that it's now being offered routinely in several countries despite doubts over safety. Studies have found anywhere from 10% to 35% of participants have to withdraw due to significant or repeated reactions, and often fail to document "subjective" symptoms like nausea and abdominal pain.
"A patient may therefore experience significant persistent abdominal cramps but this might be deemed 'tolerated' according to outcome definitions that require the presence of objective symptoms," the report states.
Brockman told the Voice she had been asking her allergist for years about oral immunotherapy for Rachel, and his response was that oral immunotherapy as it exists today amounts to "cowboy medicine," with everyone taking a different approach. She said the phrase stuck in her head -- the idea of clinics experimenting on her child -- but she is convinced that Whitney Block's clinic is different, based on breakthrough studies at Stanford and years of practical experience.
"She's not a rogue allergist," Brockman said.
A path to acceptance
It's a wonder that immunotherapy has been known and documented for more than 100 years, yet largely remains in an experimental state today, said Dr. Jayson Dallas, the CEO of Aimmune.
Peanut allergies alone affect 1.6 million kids in the United States between the ages of 4 and 17, and yet the "wholly unfulfilling" solution today is to pick up a prescription for two EpiPens and try not to die, he said.
Dallas, through his Brisbane-based company, is hoping to take a major step towards normalizing immunotherapy with AR101, a peanut pill regimen that will clear dosing, pacing and -- most importantly -- approval from the FDA. After an unexpected delay caused by the government shutdown, the hope now is to get approval by January 2020.
"This is the first time a food allergy treatment is being reviewed by the FDA," Dallas said.
Patients using the desensitization pills would start out with a minuscule 0.5 milligrams of peanuts and slowly ramp up to 300 milligrams over the course of six months. Appointments to increase the dosage are scheduled every two weeks in a clinical environment, and should provide enough tolerance for patients to handle ingesting three peanuts.
The so-called Biologics License Application process is typically a regulatory pipeline for pharmaceuticals rather than food. But the FDA ultimately found that the specific mix of peanut protein and the way it was being used by Aimmune means it amounts to a therapeutic drug.
An FDA spokesperson did not respond to requests for comment.
If approved, Kim said he believes immunotherapy clinics will face "immense pressure" to start using AR101 instead of doing their own thing, if only because patients are seeking an FDA seal of approval.
Block said she isn't so sure about that. AR101 and its standardized dosing will not be flexible based on each patient's tolerance, making it difficult to treat people with varying levels of sensitivity. She also points out that patients allergic to other allergens -- like tree nuts, milk and eggs -- are still out of luck, and the release of AR101 may leave physicians feeling emboldened to start experimenting in a field where accidental reactions are a real possibility.
"It kind of scares me that allergists are going to just start using AR101 and think they have all of the knowledge needed to go off and do what they want with all the other (food) allergens, and someone is going to do something stupid," she said.
Block's advice to parents considering oral immunotherapy is to look at the clinician's experience, including where they were trained in treating food allergies and how they came up with the dosing protocols. Clinics should also have a clear plan for what to do if a patient has an allergic reaction, and how fast a designated person on call will respond if a reaction does occur.